We propose a coordinated and highly interactive program for the investigation of the immunology and immunotherapy of human cancer. Four project areas are proposed; each relates to the central theme of developing new means to utilize the immune system in the treatment of cancer patients. Project I will define and characterize immunological factors that can suppress tumor growth. Human monoclonal anti-idiotype antibodies and human lymphoid cell clones specific for human tumor-associated antigens will be developed and characterized. Project II will expand on previous findings that circulating immune complexes in cancer patients include complexes containing immunochemically definable tumor-associated antigens. The antigens will be further purified and characterized, and sensitive and specific immunoassays will be developed. Project III is a systematic study of the use of active specific immunotherapy for the treatment of malignant melanoma. Immunization with allogeneic and autologous tumor-cell vaccines will be extensively investigated. Host modification will be focused on the augmentation of tumor associated humoral immune responses by the ablation of cellular suppressor functions of the expansion of cellular helper functions. Project IV will focus on natural killer cells and their regulation in cancer patients. The effects of alloimmunization, interferon, or interleukin-2 therapy on NK- precursors and suppressors will be studied. These projects share many areas of technology, a common patient population, and a team of experienced investigators who are highly established in their respective fields.